DESCRIPTION: Boron neutron capture therapy (BNCT) provides an alternative radiation treatment for various cancers. The therapy requires selective accumulation of B-10-containing compounds in the tumor before irradiation with neutrons. Since several tumor-seeking boron compounds (such as sodium borocaptate, BSH) have been developed, suitable drug carrier systems may also be explored to enhance the targeting delivery. Many studies have indicated the use of small liposomes as a good carrier system for tumor targeting delivery with minimized drug side effects. The accumulation of drug carried by liposomes in tumors apparently involves extravasation, presumably due to increased leaky vasculature of the rapidly growing tumor mass. However, the disadvantage of conventional liposomes is that before they can be taken up by the tumor, they are rapidly cleared from the circulation via uptake by the reticuloendothelial system (RTES). A prolonged blood-circulation liposome formulation may overcome this problem. It is the main goal of this proposed research to investigate a polyethylene glycol (PEG)-modified liposome formulation of BSA for BNCT. BSH is one of the primary boron containing compounds in the BNCT research programs worldwide. The hypothesis to be tested is that the PEG-modified liposome formulation may extend the blood-circulation time of BSH due to reduced uptake by RES. Therefore, it may be better than the conventional liposomes as a drug carrier system for targeting delivery. Since the previous submission of the application, a mouse experiment involving conventional liposomes and PEG-modified liposomes of BSH has been conducted and a reduced RES uptake of the latter was observed. To further test the hypothesis, several PEG modified liposome formulations of BSH will be prepared. The pharmacokinetic behaviors of BSH delivered by these liposome formulations will be studied in rats to examine their blood-residence times and other pharmacokinetic parameters. The effect of PEG modification on the cellular uptake of BSH from the PEG-liposomes compared to the conventional liposomes will be studied. The biodistribution (especially the tumor uptake) of BSH delivered by the PEG-modified liposome formulation of BSH is a new application of the liposome technique and the development may lead to a better application of the BNCT treatment.